Provided herein is an improved process for the preparation of 2-amino-5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidine from 4-amino-2,5-dimethoxypyrimidine.
U.S. Pat. No. 8,143,395 B2 describes a method to manufacture certain 2-amino-5,8-dialkoxy[1,2,4]triazolo[1,5-c]pyrimidines that avoids hydrazine and cyanogen halide. In this process a 4-amino-2,5-dialkoxypyrimidine is reacted with, for example, ethoxy carbonyl-isothiocyanate (S═C═N—CO2Et) in a polar aprotic solvent to provide an ethyl[(2,5-dialkoxypyrimidin-4-yl)amino]carbonothioylcarbamate, which in turn is reacted with an hydroxylamine salt in the presence of a base to provide an ethyl[(2,5-dialkoxypyrimidin-4-yl)amino](hydroxyimino)methylcarbamate. Upon heating, this intermediate cyclizes via a series of reactions to provide the desired 2-amino-5,8-dialkoxy[1,2,4]triazolo[1,5-c]-pyrimidines. While the process described in U.S. Pat. No. 8,143,395 B2 eliminates the need for hydrazine and cyanogen halide, it introduces new challenges with respect to the generation of several equivalents of gaseous by-products. It would be desirable to have a more streamlined and safer process by which to produce 2-amino-5,8-dialkoxy[1,2,4]-triazolo[1,5-c]pyrimidines.